Summary Both adverse childhood experiences (ACEs) and shorter telomere length (TL) have been associated with chronic disease in adulthood, however, few researchers have examined effects of ACEs on TL early in the life course or at sensitive periods in development, limiting opportunities for earlier and/or developmentally timed intervention. Additionally, studies focused on hypothesized biological and psychological mechanisms through which ACEs contribute to shortening of telomeres are limited. Moreover, the effect of contextual exposures outside of adolescents' neighborhood on TL has not been examined. In our previous research, we found that adolescents spend 35% of their waking time outside of their residential census tract, thus the effect of contextual exposures encompassing adolescents' neighborhood and other routine locations (e.g. school, peers, activities, etc.), known as their “activity space,” on TL has not been examined. Our study will add to the evidence on the relationship between ACEs and TL in adolescence by examining ACEs occurring at specific developmental periods (birth, early childhood, middle childhood, and adolescence) as well as cumulatively. We will also investigate biological (HPA axis; hair cortisol) and psychological (depressive and anxious symptoms) stress pathways through which ACEs may affect TL. Moreover, we will also use novel activity space data to examine relationships between adolescents' exposure to contemporary individual and sociospatial adversity and TL. Our specific aims are to examine: patterns of ACEs occurring across childhood and adolescence (birth, 0-5 years, 6-10 years, and 11 to 17 years) and their effect on adolescent biological stress, psychological distress, and TL; relationships between biological stress and TL and psychological distress and TL; the extent to which biological stress and psychological distress mediate the relationship between patterns of child/adolescent ACEs and adolescent TL; patterns of contemporary individual and activity space ACEs during adolescence and their effect on adolescent biological stress, psychological distress, and TL, accounting for ACEs prior to age 11 years; and the extent to which biological stress and psychological distress mediate the relationship between patterns of contemporary individual and activity space ACEs and adolescent TL, accounting for ACEs prior to age 11 years. In the analysis of each aim we will explore sex as a moderator of the hypothesized relationships. The study is a secondary analysis of data collected from two NIH funded studies of 1,018 adolescents. Study variables will be constructed from existing data and analyzed using descriptive statistics for data distribution, identify outliers, conduct data transformation if needed to achieve normality, and summarize subject characteristics. We will use latent class analysis and multiple linear regressions models for hypothesis testing. Our approach will identify sub-groups of ACEs across childhoo...